News from the Field

NCI Opens New Door for CAM Research with Small Grant Program

For the first time, NCI is offering grant awards – R03 grants – for researchers interested in starting small pilot and feasibility studies of CAM therapies and practices. These studies can generate data needed for conducting larger scientific studies of CAM in the future.

Through the initial R03 Program Announcement (PA) released last spring, NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM) seeks to “encourage investigators to initiate research in areas not typically explored” in larger studies funded by more rigorous grant mechanisms, such as R01 and R21 awards.

Isis Mikhail, M.D., M.P.H., Dr.P.H., who proposed and is directing the R03 program for OCCAM, said, “These are small grants of up to $50,000 a year for two-years in direct costs. They’re mainly aimed at pilot and feasibility studies for CAM. If investigators have a CAM therapy to explore, they can start a pilot project to develop the necessary background information to help them move forward to apply for a larger grant such as an R01 grant. R03s do not require that you already have background data. It’s actually a tool to develop such data.”

She added, “It really opens another door for studies of CAM remedies that haven’t had the opportunity to acquire sufficient pilot data and may hopefully, eventually help us to find some new CAM treatments or therapies for cancer.”

Dr. Mikhail noted that the PA spotlights CAM therapies identified by NCI’s Best Case Series Program as ideal candidates for pilot testing under the R03 grant mechanism. Examples of such therapeutic regimens include the treatment approach of the P. Banerji Homeopathic Research Foundation, insulin potentiation therapy, and macrobiotic lifestyle as per the Kushi Institute. Research of these approaches is high-risk and previous efforts to stimulate investigations via single contract mechanisms have not been fruitful.

“Researchers now have a second option with the R03 mechanism to collect more data to expand the cases from best case series submissions; maybe do a small clinical trial or a study of any type of design they see fit,” Dr. Mikhail continued. “This provides them a ‘Plan B’ that may allow an opportunity to show if their CAM approach has promise.”

In 2008, OCCAM staff worked together to identify important research areas and gaps. OCCAM identified three areas of research for its focused efforts for the R03 and other grant programs. These include: 1) identifying novel therapeutics in the pharmacopeia of traditional medical systems as defined by the World Health Organization; 2) using complementary approaches to improve the therapeutic ratio of standard and investigational anti-cancer therapies; and 3) research on lifestyle modifications (e.g., diet, exercise, mind-body approaches) for their impact on cancer outcomes (e.g., response to conventional cancer therapy, survival).

NCI’s PA for the R03 CAM awards is generating considerable interest among researchers and CAM practitioners, thanks to OCCAM’s efforts to advertise the program in various medical, CAM and integrative medicine journals. “I’ve received many phone calls and e-mails recently, so our PA is starting to get noticed,” said Dr. Mikhail.

“With this PA we intend to promote the establishment of collaborations between researchers and CAM practitioners,” she continued. “We’re also open to international applicants, for example, Chinese, Indian, and Korean researchers. I’ve received phone calls from scientists in Germany and Canada. We’re really quite excited about this program!”

If the R03 program generates good projects, there will be a number of follow-up options for researchers, Dr. Mikhail explained. “If an R03 grantee is successful with a small, pilot study, it will help them move forward with a larger study, possibly an R01. If the funds for a successful R03 grant application are used to document a clinical case series of patients treated with an unconventional cancer therapy, then that series could be submitted to the NCI Best Case Series Program, which seeks to identify approaches that warrant NCI-initiated research.”

Application deadlines for the R03 grants are on the regular rolling trimester schedule for all NIH grants, with deadlines in February, June, and October. For more information about this announcement, please refer to the PA announcement at http://grants.nih.gov/grants/guide/pa-files/PA-09-168.html or contact Dr. Mikhail at mikhaili@mail.nih.gov.

Recovery Act Adds CAM Supplements to OCCAM’s Portfolio

Six months after President Obama signed the American Recovery and Reinvestment Act of 2009 (Recovery Act), OCCAM funded three new supplements to grants in its portfolio. Dr. Fazlul Sarkar (Wayne State University), Dr. Rakesh Srivastava (University of Texas Health Center at Tyler), and Dr. Yung-Chi Cheng (Yale University) were awarded supplements to their parent grants.

The Recovery Act was developed as an effort to jumpstart our economy, create or save millions of jobs, and put a down payment on addressing long-neglected research challenges in our country. NIH received $10.4 billion to spend over two years on research and infrastructure. NIH research funding awarded through the Recovery Act was selected based on the ability to: promote job creation; develop the economy; accelerate the pace and achievement of scientific research; and have high impact on the field of research.

Two of OCCAM’s Recovery Act supplements were chosen, in part, because they address a highly significant area of research – pancreatic cancer, which is a cancer with both a very poor prognosis and 5-year survival rate.

Dr. Sarkar was awarded a supplement to a parent study, which examines B-DIM – a natural non-toxic agent – for its chemopreventive and chemotherapeutic effects against pancreatic cancer. The parent grant seeks to elucidate the mechanistic role of several signaling molecules in pancreatic cancer and further assess the role of B-DIM for the inhibition of pancreatic cancer cell growth, migration, and angiogenesis; and induction of apoptosis in vitro, and the anti-tumor activity in xeno-graft as well as in two distinct transgenic animal models of pancreatic cancer. The supplement will allow Dr. Sarkar to perform novel experiments for assessing the expression of miRNA and its relationship to gene expression profiles of target genes by microarray of pancreatic tumors, with and without B-DIM treatment using 2 distinct transgenic animal models.

(Grant number: 3R01CA131151-02S1)

Dr. Srivastava has been awarded a supplement to a parent grant studying the green tea polyphenol epigallocatechin-3-gallate (EGCG). EGCG is a natural non-toxic product, which exerts significant inhibitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The parent grant is investigating whether EGCG can be used as a chemo-preventive agent against pancreatic cancer using xenograft, orthotopic and KrasG12D transgenic mouse models, and to examine the molecular mechanisms by which EGCG causes growth arrest and apoptosis in pancreatic cancer. Both these processes are not well understood. The main hypothesis of the parent grant is that EGCG will inhibit the Ras-dependent P13K/Akt and MAP kinase activities and that these two will converge to regulate FOXO transcription factors, cell growth, and apoptosis in pancreatic cancer cells.

The objective of Dr. Srivastava’s supplement is to examine how JAK/STAT3 pathway mediates chemopreventive properties of EGCG in vitro and KrasG12D transgenic mouse model in vivo. In addition, he will assess whether inhibition of STAT3 can enhance the biological effects of EGCG and gemcitabine in pancreatic cancer.

(Grant number: 3R01CA125262-02S1)

Dr. Cheng was awarded an equipment supplement to continue the work of his U01 project, which examines the mechanisms of anticancer activity of the nucleoside analog troxacitabine (L-OddC), and PHY906, a Chinese herbal mixture. The equipment supplement will replace old and unreliable equipment utilized for separation, purification, detection, and storage of RNA, DNA, protein, and small molecules and will improve the capacity to quantify and characterize protein, RNA, and DNA from small tissue samples. Replacing and upgrading the equipment will accelerate and improve the scientific research conducted.

(Grant number: 3R01CA063477-14S1)

“By allowing more in depth investigation of these research topics with more up-to-date equipment, these supplement funds will speed the progress of these scientists in the generation of their important findings, while also retaining or hiring new staff in their labs, thus contributing to our nations economic recovery,” said OCCAM’s Director Dr. Jeffrey D. White.

For more information on the Recovery Act, visit http://www.nih.gov/recovery/index.htm. To search for ARRA grants, visit http://projectreporter.nih.gov/reporter.cfm.

For more information on other CAM-related ARRA Grant Awards funded through NCI, visit http://cam.cancer.gov/research/research_arra_awards_2009.htm.